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Pharmacogenetics in Colorectal Cancer

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Pharmacogenetics: Making cancer treatment safer and more effective

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Abstract

Colorectal cancer is one of the most common tumours and a major cause of cancer death worldwide. For nearly 50 years, the cornerstone of medical treatment for colorectal cancer has been the fluoropyrimidine, 5-fluorouracil. Following the development of novel chemotherapeutic drugs (e.g. oxaliplatin, irinotecan, capecitabine) and targeted biologic agents (e.g. bevacizumab, cetuximab, panitumumab), the treatment of this disease has changed significantly over the past decade. However, inter-individual differences in response and toxicity are observed and many patients do not benefit from these anticancer agents. Identification of specific markers to maximize efficacy, to minimize toxicity and to facilitate the “individualization” of patient treatment is necessary for ethical and economic reasons.

To date, several potential biological predictive markers of efficacy and/or toxicity in colorectal cancer have been identified, but their inconsistent results in different studies complicate their application into clinical practice.

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References

  • Allan JM, Wild CP, Rollinson S et al (2001) Polymorphism in glutathione S-transferase P1 is associated with susceptibility to chemotherapy-induced leukemia. Proc Natl Acad Sci USA 98:11592–11597

    Article  PubMed  CAS  Google Scholar 

  • Allegra CJ, Jessup JM, Somerfield MR et al (2009) American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy. J Clin Oncol 27:2091–2096

    Article  PubMed  Google Scholar 

  • Amado RG, Wolf M, Peeters M et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634

    Article  PubMed  CAS  Google Scholar 

  • Amstutz U, Farese S, Aebi S, Largiadèr CR (2008) Hypermethylation of the DPYD promoter region is not a major predictor of severe toxicity in 5-fluorouracil based chemotherapy. J Exp Clin Cancer Res 27:54

    Article  PubMed  CAS  Google Scholar 

  • Ando Y, Saka H, Ando M et al (2000) Polymorphisms of UDP glucuronosyltransferase gene and irinotecan toxicity: A pharmacogenetic analysis. Cancer Res 60:6921–6926

    PubMed  CAS  Google Scholar 

  • André T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351

    Article  PubMed  Google Scholar 

  • André T, Sargent D, Tabernero J et al (2006) Current issues in adjuvant treatment of stage II colon cancer. Ann Surg Oncol 13:887–898

    Article  PubMed  Google Scholar 

  • Andreyev HJ, Norman AR, Cunningham D et al (1998) Kirsten ras mutations in patients with colorectal cancer: The multicenter “RASCAL” study. J Natl Cancer Inst 90:675–684

    Article  PubMed  CAS  Google Scholar 

  • Andreyev HJ, Norman AR, Cunningham D et al (2001) Kirsten ras mutations in patients with colorectal cancer: The ‘RASCAL II’ study. Br J Cancer 85:692–696

    Article  PubMed  CAS  Google Scholar 

  • Ahmed F, Vyas V, Cornfield A et al (1999) In vitro activation of irinotecan to SN-38 by human liver and intestine. Anticancer Res 19:2067–2071

    PubMed  CAS  Google Scholar 

  • Barber TD, Vogelstein B, Kinzler KW, Velculescu VE (2004) Somatic mutations of EGFR in colorectal cancers and glioblastomas. N Engl J Med 351:2883

    Article  PubMed  CAS  Google Scholar 

  • Ben Fredj R, Gross E, Chouchen L et al (2007) Mutational spectrum of dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population. C R Biol 330:764–769

    Article  PubMed  CAS  Google Scholar 

  • Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648

    Article  PubMed  CAS  Google Scholar 

  • Beutler E, Gelbart T, Demina A (1998) Racial variability in the UDPglucuronosyltransferase 1 (UGT1A1) promoter: A balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 95:8170–8174

    Article  PubMed  CAS  Google Scholar 

  • Bokemeyer C, Bondarenko I, Makhson A et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671

    Article  PubMed  CAS  Google Scholar 

  • Bos JL (1989) Ras oncogenes in human cancer: a review. Cancer Res 49:4682–4689

    PubMed  CAS  Google Scholar 

  • Bosma PJ, Chowdhury JR, Bakker C et al (1995) The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med 333:1171–1175

    Article  PubMed  CAS  Google Scholar 

  • Braun MS, Richman SD, Quirke P et al (2008) Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol 26:2690–2698

    Article  PubMed  CAS  Google Scholar 

  • Chabot GG (1997) Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet 33:245–259

    Article  PubMed  CAS  Google Scholar 

  • Cappuzzo F, Finocchiaro G, Rossi E et al (2008) EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol 19:717–723

    Article  PubMed  CAS  Google Scholar 

  • Carlini LE, Meropol NJ, Bever J et al (2005) UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res 11:1226–1236

    PubMed  CAS  Google Scholar 

  • Chang PM, Tzeng CH, Chen PM et al (2008) ERCC1 codon 118 C–>T polymorphism associated with ERCC1 expression and outcome of FOLFOX-4 treatment in Asian patients with metastatic colorectal carcinoma. Cancer Sci. Dec 4. [Epub ahead of print]

    Google Scholar 

  • Chung KY, Shia J, Kemeny NE et al (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810

    Article  PubMed  CAS  Google Scholar 

  • Ciotti M, Basu N, Brangi M, Owens IS (1999) Glucuronidation of 7-ethyl-10 hydroxycamptothecin (SN-38) by the human UDPglucuronosyltransferases encoded at the UGT1 locus. Biochem Biophys Res Commun 260:199–202

    Article  PubMed  CAS  Google Scholar 

  • Collie-Duguid ES, Etienne MC, Milano G, McLeod HL (2000) Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics 10:217–223

    Article  PubMed  CAS  Google Scholar 

  • Cote JF, Kirzin S, Kramar A et al (2007) UGT1A1 polymorphism can predict hematologic toxicity in patients treated with irinotecan. Clin Cancer Res 13:3269–3275

    Article  PubMed  CAS  Google Scholar 

  • Culy CR, Clemett D, Wiseman LR (2000) Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs 60:895–924

    Article  PubMed  CAS  Google Scholar 

  • Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345

    Article  PubMed  CAS  Google Scholar 

  • Danenberg PV, Langenbach RJ, Heidelberger C (1974) Structures of reversible and irreversible complexes of thymidylate synthetase and fluorinated pyrimidine nucleotides. Biochemistry 13:926–933

    Article  PubMed  CAS  Google Scholar 

  • de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    PubMed  Google Scholar 

  • De Roock W, Piessevaux H, De Schutter J et al (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508–515

    Article  PubMed  Google Scholar 

  • Desch CE, Benson AB 3rd, Somerfield MR et al (2005) Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 23:8512–8519

    Article  PubMed  Google Scholar 

  • Diasio RB, Harris BE (1989) Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet 16:215–237

    Article  PubMed  CAS  Google Scholar 

  • Diasio RB, Beavers TL, Carpenter JT (1988) Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J Clin Invest 81:47–51

    Article  PubMed  CAS  Google Scholar 

  • Diasio RB, Johnson MR (1999) Dihydropyrimidine dehydrogenase: its role in 5-fluorouracil clinical toxicity and tumor resistance. Clin Cancer Res 5:2672–2673

    PubMed  CAS  Google Scholar 

  • Di Fiore F, Blanchard F, Charbonnier F et al (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer 96:1166–1169

    Article  PubMed  CAS  Google Scholar 

  • Douillard JY, Cunningham D, Roth AD et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicenter randomised trial. Lancet 355:1041–1047

    Article  PubMed  CAS  Google Scholar 

  • Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2009) Recommendations from the EGAPP Working Group: can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? Genet Med 11:15–20

    Article  CAS  Google Scholar 

  • Ezzeldin HH, Lee AM, Mattison LK, Diasio RB (2005) Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Clin Cancer Res 11:8699–8705

    Article  PubMed  CAS  Google Scholar 

  • Ferlay J, Autier P, Boniol M et al (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592

    Article  PubMed  CAS  Google Scholar 

  • Ferraldeschi R, Minchell LJ, Roberts SA et al (2009) UGT1A1 * 28 genotype predicts gastrointestinal toxicity in patients treated with intermediate dose irinotecan. Pharmacogenomics 10:733–739

    Article  PubMed  CAS  Google Scholar 

  • Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611

    Article  PubMed  CAS  Google Scholar 

  • Figueredo A, Coombes ME, Mukherjee S (2008) Adjuvant therapy for completely resected stage II colon cancer. Cochrane Database Syst Rev 16:CD005390

    Google Scholar 

  • Fleming RA, Milano GA, Gaspard MH et al (1993) Dihydropyrimidinedehydrogenase activity in cancer patients. Eur J Cancer 29A:740–744

    Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186

    Article  PubMed  CAS  Google Scholar 

  • Frattini M, Saletti P, Romagnani E et al (2007) PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer 97:1139–1145

    Article  PubMed  CAS  Google Scholar 

  • Freeman DJ, Juan T, Reiner M et al (2008) Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer 7:184–190

    Article  PubMed  CAS  Google Scholar 

  • Gagne JF, Montminy V, Belanger P et al (2002) Common human UGT1A polymorphisms and the altered metabolism of irinotecan active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). Mol Pharmacol 62:608–617

    Article  PubMed  CAS  Google Scholar 

  • Garm Spindler KL, Pallisgaard N, Rasmussen AA et al (2009) The importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer. Ann Oncol 20:879–884

    Article  PubMed  Google Scholar 

  • Gebhardt F, Zanker KS, Brandt B (1999) Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat intron 1. J Biol Chem 274:13176–13180

    Article  PubMed  CAS  Google Scholar 

  • Giacchetti S, Perpoint B, Zidani R et al (2000) Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 18:136–147

    PubMed  CAS  Google Scholar 

  • Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544

    Article  PubMed  CAS  Google Scholar 

  • Goldstein NS, Armin M (2001) Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92:1331–1346

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez FJ, Fernandez-Salguero P(1995) Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol Sci 16:325–327

    Article  PubMed  CAS  Google Scholar 

  • Gosens MJ, Moerland E, Lemmens VP et al (2008) Thymidylate synthase genotyping is more predictive for therapy response than immunohistochemistry in patients with colon cancer. Int J Cancer 123:1941–1949

    Article  PubMed  CAS  Google Scholar 

  • Graziano F, Ruzzo A, Loupakis F et al (2008a) Liver-only metastatic colorectal cancer patients and thymidylate synthase polymorphisms for predicting response to 5-fluorouracil-based chemotherapy. Br J Cancer 99:716–721

    Article  PubMed  CAS  Google Scholar 

  • Graziano F, Ruzzo A, Loupakis F et al (2008b) Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J Clin Oncol 26:1427–1434

    Article  PubMed  CAS  Google Scholar 

  • Grothey A, Sargent D, Goldberg RM, Schmoll HJ (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol 22:1209–1214

    Article  PubMed  CAS  Google Scholar 

  • Grothey A, McLeod HL, Green EM, et al (2005) Glutathione S-transferase P1 I105V (GSTP1 I105V) polymorphism is associated with early onset of oxaliplatin-induced neurotoxicity. 2005 ASCO Annual Meeting Proceedings; May 13–17, 2005; Orlando, (FL)

    Google Scholar 

  • Gupta E, Lestingi TM (1994) Metabolic fate of irinotecan in humans: correlation of glucorinidation with diarrhea. Cancer Res 54:3723–3725

    PubMed  CAS  Google Scholar 

  • Gusella M, Bolzonella C, Crepaldi G et al (2006) A novel G/C single-nucleotide polymorphism in the double 28-bp repeat thymidylate synthase allele. Pharmacogenomics J 6:421–424

    Article  PubMed  CAS  Google Scholar 

  • Hall D, Ybazeta G, Destro-Bisol G et al (1999) Variability at the uridine diphosphate glucuronosyltransferase 1A1 promoter in human populations and primates. Pharmacogenetics 9:591–599

    Article  PubMed  CAS  Google Scholar 

  • Hamdy SI, Hiratsuka M, Narahara K et al (2002) Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population. Br J Clin Pharmacol 53:596–603

    Article  PubMed  CAS  Google Scholar 

  • Hebbar M, Wacrenier A, Desauw C et al (2006) Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer. Anticancer Drugs 17:855–857

    Article  PubMed  CAS  Google Scholar 

  • Hecht JR, Mitchell EP, Baranda J et al (2008) Panitumumab (pmab) efficacy in patients (pts) with metastatic colorectal cancer (mCRC) with low or undetectable levels of epidermal growth factor receptor (EGFr): Final efficacy and KRAS analyses. ASCO Gastrointestinal Cancers Symposium. January 25–27, 2008; Orlando, FL

    Google Scholar 

  • Heinemann V, Stintzing S, Kirchner T, Boeck S, Jung A (2008) Clinical relevance of EGFR- and KRAS-status in colorectal cancer patients treated with monoclonal antibodies directed against the EGFR. Cancer Treat Rev 35:262–271

    Article  PubMed  CAS  Google Scholar 

  • Hoff PM, Ansari R, Batist G et al (2001) Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 19:2282–2292

    PubMed  CAS  Google Scholar 

  • Horie N, Aiba H, Oguro K, Hojo H, Takeishi K (1995) Functional analysis and DANN polymorphism of the tandemly repeated sequences in the 5’-terminal regulatory region of the human gene for thymidylate synthase. Cell Struct Funct 20:191–197

    Article  PubMed  CAS  Google Scholar 

  • Hoskins JM, Goldberg RM, Qu P et al (2007) UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst 99:1290–1295

    Article  PubMed  CAS  Google Scholar 

  • Hsiao HH, Yang MY, Chang JG et al (2004) Dihydropyrimidine dehydrogenase pharmacogenetics in the Taiwanese population. Cancer Chemother Pharmacol 53:445–451

    Article  PubMed  CAS  Google Scholar 

  • Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  PubMed  CAS  Google Scholar 

  • Iacopetta B, Grieu F, Joseph D, Elsaleh H (2001) A polymorphism in the enhancer region of the thymidylate synthase promoter influences the survival of colorectal cancer patients treated with 5-fluorouracil. Br J Cancer 85:827–830

    Article  PubMed  CAS  Google Scholar 

  • Innocenti F, Ratain MJ (2002) Update on pharmacogenetics in cancer chemotherapy. Eur J Cancer 38:639–644

    Article  PubMed  CAS  Google Scholar 

  • Innocenti F, Ratain MJ (2006) Pharmacogenetics of irinotecan: clinical perspectives on the utility of genotyping. Pharmacogenomics 7:1211–1221

    Article  PubMed  CAS  Google Scholar 

  • Innocenti F, Undevia SD, Iyer L et al (2004) Genetic variants in the UDPglucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388

    Article  PubMed  CAS  Google Scholar 

  • Iyer L, Das S, Janisch L et al (2002) UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J 2:43–47

    Article  PubMed  CAS  Google Scholar 

  • Jakobsen A, Nielsen JN, Gyldenkerne N, Lindeberg J (2005) Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity. J Clin Oncol 2:1365–1369

    Article  CAS  Google Scholar 

  • Johnson MR, Hageboutros A, Wang K, High L, Smith JB, Diasio RB (1999) Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil. Clin Cancer Res 5:2006–2011

    PubMed  CAS  Google Scholar 

  • Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357:2040–2048

    Article  PubMed  CAS  Google Scholar 

  • Kabbinavar FF, Hambleton J, Mass RD et al (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23:3706–3712

    Article  PubMed  CAS  Google Scholar 

  • Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR (2000) Genetic lessons of bilirubin uridine-diphosphoglucuronate glucuronosyl-transferase (UGT1A1) causing Crigler–Najjar and Gilbert’s syndromes: correlation of genotype to phenotype. Hum Mutat 16:297–306

    Article  PubMed  CAS  Google Scholar 

  • Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765

    Article  PubMed  CAS  Google Scholar 

  • Kaneda S, Nalbantoglu J, Takeishi K et al (1990) Structural and functional analysis of the human thymidylate synthase gene. J Biol Chem 265:20277–20284

    PubMed  CAS  Google Scholar 

  • Kawakami K, Omura K, Kanehira E, Watanabe Y (1999) Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res 19:3249–3252

    PubMed  CAS  Google Scholar 

  • Kawakami K, Salonga D, Park JM et al (2001) Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression. Clin Cancer Res 7:4096–4101

    PubMed  CAS  Google Scholar 

  • Kawakami K, Watanabe G (2003) Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer Res 15:6004–6007

    Google Scholar 

  • Kweekel DM, Gelderblom H, Guchelaar HJ (2005). Pharmacology of oxaliplatin and the use of pharmacogenomics to individualize therapy. Cancer Treat Rev 31:90–105

    Article  PubMed  CAS  Google Scholar 

  • Kweekel D, Guchelaar HJ, Gelderblom H (2008a) Clinical and pharmacogenetic factors associated with irinotecan toxicity. Cancer Treat Rev 34:656–669

    Article  PubMed  CAS  Google Scholar 

  • Kweekel DM, Gelderblom AJ, van der Straaten T et al (2008b) UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer – a Dutch Colorectal Cancer Group study. Br J Cancer 99:275–282

    Article  PubMed  CAS  Google Scholar 

  • Kweekel DM, Gelderblom H, Antonini NF et al (2009) Glutathione-S-transferase pi (GSTP1) codon 105 polymorphism is not associated with oxaliplatin efficacy or toxicity in advanced colorectal cancer patients. Eur J Cancer 45:572–578

    Article  PubMed  CAS  Google Scholar 

  • Kuebler JP, Wieand HS, O’Connell MJ et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 25:2198–2204

    Article  PubMed  CAS  Google Scholar 

  • Langenbach RJ, Danenberg PV, Heidelberger C (1972) Thymidylate synthetase: mechanism of inhibition by 5-fluoro-2'-deoxyuridylate. Biochem Biophys Res Commun 48:1565–1571

    Article  PubMed  CAS  Google Scholar 

  • Lecomte T, Ferraz JM, Zinzindohoué F et al (2004) Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy. Clin Cancer Res 10:5880–5888

    Article  PubMed  CAS  Google Scholar 

  • Lecomte T, Landi B, Beaune P, Laurent-Puig P, Loriot MA (2006) Glutathione Stransferase P1 polymorphism (Ile105Val) predicts cumulative neuropathy in patients receiving oxaliplatin-based chemotherapy. Clin Cancer Res 12:3050–3056

    Article  PubMed  CAS  Google Scholar 

  • Le Morvan V, Smith D, Laurand A et al (2007) Determination of ERCC2 Lys751Gln and GSTP1 Ile105Val gene polymorphisms in colorectal cancer patients: relationships with treatment outcome. Pharmacogenomics 8:1693–1703

    Article  PubMed  Google Scholar 

  • Lenz HJ, Van Cutsem E, Khambata-Ford S et al (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24:4914–4921

    Article  PubMed  CAS  Google Scholar 

  • Lincz LF, Scorgie FE, Garg MB, Ackland SP (2007) Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele. Int J Cancer 120:1930–1934

    Article  PubMed  CAS  Google Scholar 

  • Lievre A, Bachet JB, Le Corre D et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995

    Article  PubMed  CAS  Google Scholar 

  • Lievre A, Bachet JB, Boige V et al (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 26:374–379

    Article  PubMed  CAS  Google Scholar 

  • Liu W, Innocenti F, Wu MH et al (2005) A functional common polymorphism in a Sp1 recognition site of the epidermal growth factor receptor gene promoter. Cancer Res 65:46–53

    PubMed  CAS  Google Scholar 

  • Lo HW, Ali-Osman FG (2007) Genetic polymorphism and function of glutathione S-transferases in tumor drug resistance. Curr Opin Pharmacol 7:367–374

    Article  PubMed  CAS  Google Scholar 

  • Lopez ME, Kobrin MS, Moriai T et al (1996) Single strand conformation polymorphism analysis of the epidermal growth factor receptor at codon 497. Pancreas 12:216–220

    Article  PubMed  CAS  Google Scholar 

  • Lu Z, Zhang R, Diasio RB (1993) Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res 53:5433–5438

    PubMed  CAS  Google Scholar 

  • Lurje G, Nagashima F, Zhang W et al (2008) Polymorphisms in cyclooxygenase-2 and epidermal growth factor receptor are associated with progression-free survival independent of K-ras in metastatic colorectal cancer patients treated with single-agent cetuximab. Clin Cancer Res 14:7884–7895

    Article  PubMed  CAS  Google Scholar 

  • Lyss AP, Lilenbaum RC, Harris BE, Diasio RB (1993) Severe 5- fluorouracil toxicity in a patient with decreased dihydropyrimidine dehydrogenase activity. Cancer Invest 11:239–240

    Article  PubMed  CAS  Google Scholar 

  • Mandola MV, Stoehlmacher J, Muller-Weeks S et al (2003) A novel single nucleotide polymorphism within the 5_ tandem repeat polymorphism of the thymidylate synthase gene abolishes USF-1 binding and alters transcriptional activity. Cancer Res 63:2898–2904

    PubMed  CAS  Google Scholar 

  • Mandola MV, Stoehlmacher J, Zhang W et al (2004) A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 14:319–327

    Article  PubMed  CAS  Google Scholar 

  • Marcuello E, Altés A, del Rio E et al (2004a) Single nucleotide polymorphism in the 5′ tandem repeat sequences of thymidylate synthase gene predicts for response to fluorouracil-based chemotherapy in advanced colorectal cancer patients. Int J Cancer 112:733–737

    Article  PubMed  CAS  Google Scholar 

  • Marcuello E, Altes A, Menoyo A et al (2004b) UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer 91:678–682

    PubMed  CAS  Google Scholar 

  • Marsh S, McKay JA, Cassidy J, McLeod HL (2001) Polymorphism in the thymidylate synthase promoter enhancer region in colorectal cancer. Int J Oncol 19:383–386

    PubMed  CAS  Google Scholar 

  • Marsh S, McLeod HL (2004) Pharmacogenetics of irinotecan toxicity. Pharmacogenomics 5:835–843

    Article  PubMed  CAS  Google Scholar 

  • Marsh S (2005) Pharmacogenetics of colorectal cancer. Expert Opin Pharmacother 6:2607–2616

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Balibrea E, Manzano JL et al (2007) Combined analysis of genetic polymorphisms in thymidylate synthase, uridine diphosphate glucoronosyltransferase and X-ray cross complementing factor 1 genes as a prognostic factor in advanced colorectal cancer patients treated with 5-fluorouracil plus oxaliplatin or irinotecan. Oncol Rep 17:637–645

    PubMed  CAS  Google Scholar 

  • Massacesi C, Terrazzino S, Marcucci F et al (2006) Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer 106:1007–1016

    Article  PubMed  CAS  Google Scholar 

  • Matsui T, Omura K, Kawakami K, Morita S, Sakamoto J (2006) Genotype of thymidylate synthase likely to affect efficacy of adjuvant 5-FU based chemotherapy in colon cancer. Oncol Rep 16:1111–1115

    PubMed  CAS  Google Scholar 

  • McLeod HL, Parodi L, Sargent DJ et al (2006) UGT1A1*28, toxicity and outcome in advanced colorectal cancer:results from Trial N9741. 2006 ASCO Annual Meeting Proceedings; June 2–6, 2006; Atlanta, (GA)

    Google Scholar 

  • Merkel S, Wein A, Günther K et al (2001) High-risk groups of patients with stage II colon carcinoma. Cancer 92:1435–1443

    Article  PubMed  CAS  Google Scholar 

  • Messersmith WA, Hidalgo M (2007) Panitumumab, a monoclonal anti epidermal growth factor receptor antibody in colorectal cancer: another one or the one? Clin Cancer Res 13:4664–4666

    Article  PubMed  CAS  Google Scholar 

  • Meta-analysis Group in Cancer (1998a) Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 16:301–308

    Google Scholar 

  • Meta-Analysis Group In Cancer (1998b) Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. J Clin Oncol 16:3537–3541

    Google Scholar 

  • Milano G, Etienne MC, Pierrefite V, Barberi-Heyob M, Deporte-Fety R, Renee N (1999) Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity. Br J Cancer 79:627–630

    Article  PubMed  CAS  Google Scholar 

  • Milano G, Etienne-Grimaldi MC, Dahan L et al (2008) Epidermal growth factor receptor (EGFR) status and K-Ras mutations in colorectal cancer. Ann Oncol 19:2033–2038

    Article  PubMed  CAS  Google Scholar 

  • Monaghan G, Ryan M, Seddon R et al (1996) Genetic variation in bilirubin UDP glucuronosyltransferase gene promoter and Gilbert’s syndrome. Lancet 347:578–581

    Article  PubMed  CAS  Google Scholar 

  • Monzo M, Moreno I, Navarro A et al (2007) Single nucleotide polymorphisms in nucleotide excision repair genes XPA, XPD, XPG and ERCC1 in advanced colorectal cancer patients treated with first-line oxaliplatin/fluoropyrimidine. Oncology 72:364–370

    Article  PubMed  CAS  Google Scholar 

  • Moreno V, Gemignani F, Landi S et al (2006) Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res 12:2101–2108

    Article  PubMed  CAS  Google Scholar 

  • Morel A, Boisdron-Celle M, Fey L, Lainé-Cessac P, Gamelin E (2007) Identification of a novel mutation in the dihydropyrimidine dehydrogenase gene in a patient with a lethal outcome following 5-fluorouracil administration and the determination of its frequency in a population of 500 patients with colorectal carcinoma. Clin Biochem 40:11–17

    Article  PubMed  CAS  Google Scholar 

  • Moroni M, Veronese S, Benvenuti S et al (2005) Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study. Lancet Oncol 6:279–286

    Article  PubMed  CAS  Google Scholar 

  • Nagahara H, Mimori K, Ohta M et al (2005) Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. Clin Cancer Res 11:1368–1371

    Article  PubMed  CAS  Google Scholar 

  • Ng K, Zhu AX (2008) Targeting the epidermal growth factor receptor in metastatic colorectal cancer. Crit Rev Oncol Hematol 65:8–20

    Article  PubMed  Google Scholar 

  • Ogino S, Meyerhardt JA, Cantor M et al (2005) Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin Cancer Res 11:6650–6656

    Article  PubMed  CAS  Google Scholar 

  • O’Neil BH, Tepper JE (2007) Current options for the management of rectal cancer. Curr Treat Options Oncol 8:331–338

    Article  PubMed  Google Scholar 

  • Palomaki GE, Bradley LA, Douglas MP et al (2009) Can UGT1A1 genotyping reduce morbidity and mortality in patients with metastatic colorectal cancer treated with irinotecan? An evidence-based review. Genet Med 11:21–34

    Article  PubMed  CAS  Google Scholar 

  • Paré L, Marcuello E, Altés A et al (2008) Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy. Br J Cancer 99:1050–1055

    Article  PubMed  CAS  Google Scholar 

  • Park DJ, Stoehlmacher J, Zhang W, Tsao-Wei DD, Groshen S, Lenz HJ (2001) A Xeroderma pigmentosum group D gene polymorphism predicts clinical outcome to platinum-based chemotherapy in patients with advanced colorectal cancer. Cancer Res 61:8654–8658

    PubMed  CAS  Google Scholar 

  • Park DJ, Stoehlmacher J, Zhang W, Tsao-Wei D, Groshen S, Lenz HJ (2002a) Thymidylate synthase gene polymorphism predicts response to capecitabine in advanced colorectal cancer. Int J Colorectal Dis 17:46–49

    Article  PubMed  Google Scholar 

  • Park DJ, Stoehlmacher J, Zhang W, Tsao-Wei D, Groshen S, Lenz H-J (2002b) ERCC1 polymorphism is associated with differential ERCC1 gene expression. Proc AACR 93:1591

    Google Scholar 

  • Park DJ, Zhang W, Stoehlmacher J et al (2003) ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy. Clin Adv Hematol Oncol 1:162–166

    PubMed  Google Scholar 

  • Personeni N, Fieuws S, Piessevaux H et al (2008) Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study. Clin Cancer Res 14:5869–5876

    Article  PubMed  CAS  Google Scholar 

  • Pizzolato JF, Saltz LB (2003) The camptothecins. Lancet 361:2235–2242

    Article  PubMed  CAS  Google Scholar 

  • Prall F, Ostwald C, Schiffmann L, Barten M (2007) Do thymidylate synthase gene promoter polymorphism and the C/G single nucleotide polymorphism predict effectiveness of adjuvant 5-fluorouracil-based chemotherapy in stage III colonic adenocarcinoma? Oncol Rep 18:203–209

    PubMed  CAS  Google Scholar 

  • Premawardhena A, Fisher CA, Liu YT et al (2003) The global distribution of length polymorphisms of the promoters of the glucuronosyltransferase 1 gene (UGT1A1): Hematologic and evolutionary implications. Blood Cells Mol Dis 31:98–101

    Article  PubMed  CAS  Google Scholar 

  • Pullarkat ST, Stoehlmacher J, Ghaden V et al (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1:65–70

    Article  PubMed  CAS  Google Scholar 

  • Punt CJ, Tol J, Rodenburg CJ et al (2008) Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). 2008 ASCO Annual Meeting Proceedings; May 30-June 3, 2008; Chicago, (IL)

    Google Scholar 

  • Raida M, Schwabe W, Hausler P et al (2001) Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5′-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared with controls. Clin Cancer Res 7:2832–2839

    PubMed  CAS  Google Scholar 

  • Raymond E, Faivre S, Woynarowski JM et al (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12

    PubMed  CAS  Google Scholar 

  • Ridge SA, Sludden J, Wei X et al (1998) Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer. Br J Cancer 77:497–500

    Article  PubMed  CAS  Google Scholar 

  • Rivory LP, Bowles MR, Robert J, Pond SM (1996) Conversion of irinotecan (CPT-11) to its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), by human liver carboxylesterase. Biochem Pharmacol 52:1103–1111

    Article  PubMed  CAS  Google Scholar 

  • Robert J, Morvan VL, Smith D, Pourquier P, Bonnet J (2005) Predicting drug response and toxicity based on gene polymorphisms. Crit Rev Oncol Hematol 54:171–196

    Article  PubMed  Google Scholar 

  • Roth AD, Yan P, Dietrich D et al (2008) Is UGT1A1*28 homozygosity the strongest predictor for severe hematotoxicity in patients treated with 5-fluorouracil (5-FU)-irinotecan (IRI)? Results of the PETACC 3 – EORTC 40993 -SAKK 60/00 trial comparing IRI/5-FU/folinic acid (FA) to 5-FU/FA in stage II- III colon cancer (COC) patients. 2008 ASCO Annual Meeting Proceedings; May 30-June 3, 2008; Chicago, (IL)

    Google Scholar 

  • Rouits E, Boisdron-Celle M, Dumont A et al (2004) Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: A molecular and clinical study of 75 patients. Clin Cancer Res 10:5151–5159

    Article  PubMed  CAS  Google Scholar 

  • Ruzzo A, Graziano F, Loupakis F et al (2007) Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFOX-4 chemotherapy. J Clin Oncol 25:1247–1254

    Article  PubMed  CAS  Google Scholar 

  • Ruzzo A, Graziano F, Loupakis F et al (2008) Pharmacogenetic profiling in patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Pharmacogenomics J 8:278–288

    Article  PubMed  CAS  Google Scholar 

  • Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343:905–914

    Article  PubMed  CAS  Google Scholar 

  • Saltz LB, Meropol NJ, Loehrer PJ et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208

    Article  PubMed  CAS  Google Scholar 

  • Saltz L, Clarke S, Diaz-Rubio E et al (2007) Bevacizumab (Bev) in combination with XELOX or FOLFOX4: Updated efficacy results from XELOX-1/NO16966, a randomized phase III trial in first-line metastatic colorectal cancer. 2007 ASCO Annual Meeting Proceedings; June 1–5, 2007; Chicago, (IL)

    Google Scholar 

  • Sanghani SP, Quinney SK, Fredenberg TB, Davis WI, Murry DJ, Boston WF (2004). Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5- aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10- [4-(1-piperidino)-1-amino] carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug Metab Dispos 32:505–511

    Article  PubMed  CAS  Google Scholar 

  • Santi DV, McHenry CS, Sommer H (1974) Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry 13:471–481

    Article  PubMed  CAS  Google Scholar 

  • Sartore-Bianchi A, Moroni M, Veronese S et al (2007) Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab. J Clin Oncol 25:3238–3245

    Article  PubMed  CAS  Google Scholar 

  • Saunders M, Iveson T (2006) Management of advanced colorectal cancer: state of the art. Br J Cancer 95:131–138

    Article  PubMed  CAS  Google Scholar 

  • Seymour MT, Braun MS, Richman SD et al (2006) Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer (FOCUS). 2006 ASCO Annual Meeting Proceedings; June 2–6, 2006; Atlanta, (GA)

    Google Scholar 

  • Sessa C, Guibal A, Del Conte G, Rüegg C (2008) Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations? Nat Clin Pract Oncol 5:378–391

    Article  PubMed  CAS  Google Scholar 

  • Shahbazi M, Pravica V, Nasreen N et al (2002) Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 359:397–401

    Article  PubMed  CAS  Google Scholar 

  • Shankaran V, Bentrem DJ, Mulcahy MF, Bennett CL, Benson III AB (2009) Economic implications of Kras testing in metastatic colorectal cancer (mCRC). 2009 Gastrointestinal Cancers Symposium Proceedings: January 15–17, 2009; San Francisco, (CA)

    Google Scholar 

  • Shirota Y, Stoehlmacher J, Brabender J et al (2001) ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 19:4298–4304

    PubMed  CAS  Google Scholar 

  • Smith NF, Figg WD, Sparreboom A (2006) Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro 20:163–175

    Article  PubMed  CAS  Google Scholar 

  • Sobrero A, Guglielmi A (2004) Current controversies in the adjuvant therapy of colon cancer. Ann Oncol 15(Suppl 4):iv39–41

    Google Scholar 

  • Stoehlmacher J, Ghaderi V, Iobal S et al (2001) A polymorphism of the XRCC1 gene predicts for response to platinum based treatment in advanced colorectal cancer. Anticancer Res 21:3075–3079

    PubMed  CAS  Google Scholar 

  • Stoehlmacher J, Park DJ, Zhang W et al (2002) Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst 94:936–942

    Article  PubMed  CAS  Google Scholar 

  • Stoehlmacher J, Park DJ, Zhang W, et al (2004) A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 91:344–354

    PubMed  CAS  Google Scholar 

  • Sweeney C, McClure GY, Fares MY et al (2000) Association between survival after treatment for breast cancer and glutathione S-transferase P1 Ile105Val polymorphism. Cancer Res 60:5621–5624

    PubMed  CAS  Google Scholar 

  • Toffoli G, Cecchin E, Corona G et al (2006) The role of UGT1A1*28 polymorphism in the pharmacodynamics and pharmacokinetics of irinotecan in patients with metastatic colorectal cancer. J Clin Oncol 24:3061–3068

    Article  PubMed  CAS  Google Scholar 

  • Thirion P, Michiels S, Pignon JP et al (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated metaanalysis. J Clin Oncol 22:3766–3775

    Article  PubMed  CAS  Google Scholar 

  • Tsuchihashi Z, Khambata-Ford S, Hanna N, Jänne PA (2005) Responsiveness to cetuximab without mutations in EGFR. New Engl J Med 353:208–209

    Article  PubMed  CAS  Google Scholar 

  • Twelves C, Wong A, Nowacki MP et al (2005) Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 352:2696–2704

    Article  PubMed  CAS  Google Scholar 

  • Uzunkoy A, Dilmec F, Ozgonul A, van Kuilenburg AB, Akkafa F (2007) Investigation of IVS14+1G>A polymorphism of DPYD gene in a group of Turkish patients with colorectal cancer. Anticancer Res 27:3899–3902

    PubMed  CAS  Google Scholar 

  • Valentini AM, Pirrelli M, Caruso ML (2008) EGFR-targeted therapy in colorectal cancer: does immunohistochemistry deserve a role in predicting the response to cetuximab? Curr Opin Mol Ther 10:124–131

    PubMed  CAS  Google Scholar 

  • Van Cutsem E, Twelves C, Cassidy J et al (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106

    PubMed  Google Scholar 

  • Van Cutsem E, Tejpar S, Verslype C, Laurent S (2006) Challenges in the adjuvant treatment for patients with stages II and III colon cancer. ASCO educational book 2006: 179–186

    Google Scholar 

  • van Cutsem E, Nowacki M, Lang I et al (2007a) Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. 2007 ASCO Annual Meeting Proceedings; June 1–5, 2007; Chicago, (IL)

    Google Scholar 

  • van Cutsem E, Peeters M, Siena S et al (2007b) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664

    Article  PubMed  CAS  Google Scholar 

  • van Cutsem EJ, Oliveira J; ESMO Guidelines Working Group (2008a) Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up. Ann Oncol 19 (Suppl 2): ii29–30

    Google Scholar 

  • van Cutsem E, Lang I, D’haens G et al (2008b) KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (metastatic CRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. 2008 ASCO Annual Meeting Proceedings; May 30-June 3, 2008; Chicago, (IL)

    Google Scholar 

  • van Kuilenburg AB, Vreken P, Abeling NG et al (1999) Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum Genet 104:1–9

    Article  PubMed  Google Scholar 

  • van Kuilenburg AB, Haasjes J, Meinsma R, Waterham HR, Vreken P, van Gennip AH (2000) DPD deficiency in patients with severe 5-fluorouracil-associated toxicity: Identification of new mutations in the DPD gene. Clin Cancer Res 6:4705–4712

    PubMed  Google Scholar 

  • van Kuilenburg AB, Muller EW, Haasjes J et al (2001) Lethal outcome of a patient with a complete dihydropyrimidine dehydrogenase (DPD) deficiency after administration of 5- fluorouracil: frequency of the common IVS14+1G→ A mutation causing DPD deficiency. Clin Cancer Res 7:1149–1153

    PubMed  Google Scholar 

  • van Kuilenburg AB, Meinsma R, Zoetekouw L, Van Gennip AH (2002) High prevalence of the IVS14 + 1G→ A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics 12:555–558

    Article  PubMed  Google Scholar 

  • van Kuilenburg AB (2004) Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil Eur J Cancer 40:939–950

    Article  PubMed  CAS  Google Scholar 

  • Van Kuilenburg AB, Meinsma R, Beke E et al (2005) Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function. Biol Chem 386:319–324

    PubMed  Google Scholar 

  • Viguier J, Boige V, Miquel C et al (2005) ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5- fluorouracil combination chemotherapy in patients with advanced colorectal cancer. Clin Cancer Res 11:6212–6217

    Article  PubMed  CAS  Google Scholar 

  • Villafranca E, Okruzhnov Y, Dominguez MA et al (2001) Polymorphisms of the repeated sequences in the enhancer region of the thymidylate synthase gene promoter may predict downstaging afterpreoperative chemoradiation in rectal cancer. J Clin Oncol 19:1779–1786

    PubMed  CAS  Google Scholar 

  • Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA (1998) Human glutathione S-transferase P1 polymorphisms: relation- ship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis 19:275–280

    Article  PubMed  CAS  Google Scholar 

  • Wei X, McLeod HL, McMurrough J, Gonzalez FJ, Fernandez-Salguero P (1996) Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest 1:610–15.

    Article  Google Scholar 

  • Wei X, Elizondo G, Sapone A et al (1998) Characterization of the human dihydropyrimidine dehyrdogenase gene. Genomics 51:391–400

    Article  PubMed  CAS  Google Scholar 

  • Wilson MD, Ruttan CC, Koop BF, Glickman BW (2001) ERCC1: a comparative genomic perspective. Environ Mol Mutagen 38:209–215

    Article  PubMed  CAS  Google Scholar 

  • Wong R, Cunningham D (2008) Using predictive biomarkers to select patients with advanced colorectal cancer for treatment with epidermal growth factor receptor antibodies. J Clin Oncol 26:5668–5670

    Article  PubMed  CAS  Google Scholar 

  • Wood RD (1996) DNA repair in eukaryotes. Annu Rev Biochem 65:135–167

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi K, Arai Y, Kanda Y, Akagi K (2001) Germline mutation of dihydropyrimidine dehydrogenese gene among a Japanese population in relation to toxicity to 5-Fluorouracil. Jpn J Cancer Res 92:337–342

    Article  PubMed  CAS  Google Scholar 

  • Yen JL, McLeod HL (2007) Should DPD analysis be required prior to prescribing fluoropyrimidines? Eur J Cancer 43:1011–1016

    Article  PubMed  Google Scholar 

  • Yu JJ, Mu C, Lee KB, Okamoto A et al (1997) A nucleotide polymorphism in ERCC1 in human ovarian cancer cell lines and tumor tissues. Mutat Res 382:13–20

    Article  PubMed  CAS  Google Scholar 

  • Yu KH, Wang WX, Ding YM, Li H, Wang ZS (2008) Polymorphism of thymidylate synthase gene associated with its protein expression in human colon cancer. World J Gastroenterol 14:617–621

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Gordon M, Press OA et al (2006) Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab. Pharmacogenet Genomics 16:475–483

    Article  PubMed  CAS  Google Scholar 

  • Zhang K, Mack P, Wong KP (1998) Glutathione-related mechanisms in cellular resistance to anticancer drugs. Int J Oncol 12:871–82

    PubMed  CAS  Google Scholar 

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  1. Christie Hospital Manchester, Manchester, M20 4BX, UK

    Roberta Ferraldeschi

  2. Department of Medical Genetics, University of Manchester, Manchester, M13 0JH, UK

    Roberta Ferraldeschi

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    William G. Newman

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Ferraldeschi, R. (2010). Pharmacogenetics in Colorectal Cancer. In: Newman, W. (eds) Pharmacogenetics: Making cancer treatment safer and more effective. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8618-1_5

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